This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Angelman syndrome (AS) is a neurologica disorder that causes global developmental delay, minimal or absent speech, seizures, uncoodinated gait (ataxia), sleep disturbances, and other medical and behavioral difficulties. AS is caused by deficiency of disturbances, and other medical and behavioral difficulties. AS is caused by deficiency of the maternally-transmitted gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. This study has been designed to evaluate the possible therapeutic benefits of L-5-methyltetrahdydrofolate (Metafolin), vitamin B12, creatine and betaine in children with Angelman Syndrome (AS). We believe that dietary manipulation may increase global DNA methylation therefore leading to an increased methylation of the paternal chromosome and further expression of the Angelman gene using these dietary interventions causing an amelioration of the symptoms and medical problems in this disorder. All the participants for the study will include patients who have a documented molecular diagnosis of AS. The participants will be seen at Baylor College of Medicine, Children's Hospital of San Diego, Boston Children's Hospital and the Greenwood Genetics Center at 0 months, 6 months and at 12 months for follow-up. Clinical and relevant historical data will be collected during the clinical visit and examination and also by revieiwing medical and laboratory records. The enrolled subjects will be given the combination of drugs and evaluated in person at the beginning of the trial and at the end (12 months) . This information will then be entered into a HIPAA compliant clinical research database.